Multicenter phase 1 study of oral B440 vaccine in patients with metastatic urothelial carcinoma

B440 is an oral cancer vaccine, composed of recombinant Bifidobacterium longum genetically engineered to express the Wilm’s tumor 1 (WT1) tumor-associated antigen on its surface to elicit tumor-specific T-cell responses via gut-associated lymphoid tissue. A multicenter phase 1 trial in Japan evaluated B440 in patients with metastatic urothelial carcinoma (mUC) refractory to standard therapies. Twelve patients with mUC who had progressed after platinum-based chemotherapy, PD-(L)1 inhibitors, and enfortumab vedotin received oral B440 at either 800 mg (n=6) or 1600 mg (n=6) once daily for five consecutive days per week over 4 weeks. The primary endpoint was dose-limiting toxicity (DLT). No DLTs were observed. Treatment-related adverse events were grade 1, with transient IL-6 elevations reported in three patients. The disease control rate was 50%, with six patients achieving stable disease. WT1-specific T-cell responses were detected via ELISPOT assays in six patients, who showed numerically longer progression-free survival than ELISPOT-negative patients (median 117 versus 37 days). The authors conclude that B440 was safe and well tolerated. WT1-specific immune responses correlated with clinical benefit.